Exploring the role of BDNF DNA methylation and hydroxymethylation in patients with obsessive compulsive disorder

Claudio D'Addario, Fabio Bellia, Beatrice Benatti, Benedetta Grancini, Matteo Vismara, Mariangela Pucci, Vera De Carlo, Caterina Viganò, Daniela Galimberti, Chiara Fenoglio, Elio Scarpini, Mauro Maccarrone, Bernardo Dell'Osso

Research output: Contribution to journalArticle

Abstract

Obsessive-compulsive disorder (OCD) is a clinically heterogeneous neuropsychiatric condition associated with profound disability, whose susceptibility, stemming from genetic and environmental factors that intersect with each other, is still under investigation. In this perspective, we sought to explore the transcriptional regulation of Brain Derived Neurotrophic Factor (BDNF), a promising candidate biomarker in both development and etiology of different neuropsychiatric conditions, in peripheral blood mononuclear cells from OCD patients and healthy controls. In particular, we focused on BDNF gene expression and interrogated in depth DNA methylation and hydroxymethylation at gene promoters (exons I, IV and IX) in a sample of OCD patients attending a tertiary OCD Clinic to receive guidelines-recommended treatment, and matched controls. Our preliminary data showed a significant increase in BDNF gene expression and a significant correlation with changes in the two epigenetic modifications selectively at promoter exon I, with no changes in the other promoters under study. We can conclude that transcriptional regulation of BDNF in OCD engages epigenetic mechanisms, and can suggest that this is likely evoked by the long-term pharmacotherapy. It is important to underline that many different factors need to be taken into account (i.e. age, sex, duration of illness, treatment), and thus further studies are mandatory to investigate their role in the epigenetic regulation of BDNF gene. Of note, we provide unprecedented evidence for the importance of analyzing 5-hydroxymethylcytosine levels to correctly evaluate 5-methylcytosine changes.

Original languageEnglish
Pages (from-to)17-23
Number of pages7
JournalJournal of Psychiatric Research
Volume114
DOIs
Publication statusPublished - Jul 1 2019

Fingerprint

Obsessive-Compulsive Disorder
Brain-Derived Neurotrophic Factor
DNA Methylation
Epigenomics
Exons
5-Methylcytosine
Gene Expression
Genetic Predisposition to Disease
Genes
Blood Cells
Biomarkers
Guidelines
Drug Therapy
Therapeutics

Keywords

  • BDNF
  • DNA hydroxymethylation
  • DNA methylation
  • Obsessive compulsive disorder

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Exploring the role of BDNF DNA methylation and hydroxymethylation in patients with obsessive compulsive disorder. / D'Addario, Claudio; Bellia, Fabio; Benatti, Beatrice; Grancini, Benedetta; Vismara, Matteo; Pucci, Mariangela; De Carlo, Vera; Viganò, Caterina; Galimberti, Daniela; Fenoglio, Chiara; Scarpini, Elio; Maccarrone, Mauro; Dell'Osso, Bernardo.

In: Journal of Psychiatric Research, Vol. 114, 01.07.2019, p. 17-23.

Research output: Contribution to journalArticle

D'Addario, Claudio ; Bellia, Fabio ; Benatti, Beatrice ; Grancini, Benedetta ; Vismara, Matteo ; Pucci, Mariangela ; De Carlo, Vera ; Viganò, Caterina ; Galimberti, Daniela ; Fenoglio, Chiara ; Scarpini, Elio ; Maccarrone, Mauro ; Dell'Osso, Bernardo. / Exploring the role of BDNF DNA methylation and hydroxymethylation in patients with obsessive compulsive disorder. In: Journal of Psychiatric Research. 2019 ; Vol. 114. pp. 17-23.
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